ACTIVATION OF MITOGEN-ACTIVATED PROTEIN-KINASE BY EPIDERMAL GROWTH-FACTOR IN HIPPOCAMPAL-NEURONS AND NEURONAL CELL-LINES

Epidermal growth factor (EGF) functions in a bimodal capacity in the n ervous system, acting as a mitogen in neuronal stem cells and a neurot rophic factor in differentiated adult neurons. Thus, it is likely that EGF signal transduction, as well as receptor expression, differs amon g various cell types and possibly in the same cell type at different s tages of development. We used hippocampal neuronal cell lines capable of terminal differentiation to investigate changes in EGF receptor exp ression, DNA synthesis, and stimulation of mitogen-activated protein ( MAP) kinase by EGF before and after differentiation. H19-7, the line t hat was most representative of hippocampal neurons, was mitogenically responsive to EGF only before differentiation and increased in EGF bin ding after differentiation. MAP kinase was stimulated by EGF in both u ndifferentiated and differentiated cells, as well as in primary hippoc ampal cultures treated with either EGF or glutamate. These results ind icate that the activation of MAP kinase by EGF is an early signaling e vent in both mitotic and postmitotic neuronal cells. Furthermore, thes e studies demonstrate the usefulness of hippocampal cell lines as a ho mogeneous neuronal system for studies of EGF signaling or other recept or signaling mechanisms in the brain.